Project Summary/Abstract Self-reported sleep problems are common in rheumatoid arthritis (RA), but objectively-measured data on sleep are lacking. Our preliminary data provide evidence of frequent self-reported sleep problems, existence of objectively-identified sleep disturbances, and the association of those sleep disturbances with poor RA-specific health outcomes. The proposed project will address the significant knowledge gaps surrounding sleep disturbances in RA. Project aims are to: (1) identify risk factors associated with sleep disturbance and changes in sleep disturbance in individuals with RA; (2) identify the short-term and longer-term longitudinal effects of sleep disturbance and changes in sleep disturbances on health outcomes in RA; and (3) examine a biological pathway unique to RA to explain the high prevalence of sleep disturbance in RA and associations with RA outcomes. No previous studies have attempted to link the disruptions in inflammatory biomarkers and cortisol, and the concomitant peaking of RA symptoms, with sleep disturbance or with disruption of circadian rest- activity patterns. 150 individuals with RA will be enrolled and followed over 24 months. Baseline, 6- and 12- month assessments will consist of 7-nights of actigraphy monitoring to measure sleep and circadian rest- activity patterns; completion of sleep and symptom diaries; questionnaires to assess disease activity, pain, fatigue, physical activity, and symptoms of depression; blood draws for inflammatory markers; and salivary diurnal cortisol collection. Screening for other primary sleep disorders will be conducted at baseline. Follow-ups 18 and 24 months after baseline will continue monitoring sleep and outcomes with 7 nights of sleep monitoring by actigraphy and completion of sleep/symptom diaries and questionnaires. Bi-weekly telephone check-ins will be conducted to monitor use, dosage, and timing of glucocorticoids (GCs) and other medications. Innovative components of the proposed project include objective measurements of sleep, detailed examination of the role of GCs in sleep disturbance in RA, examination of the roles of inflammatory and hormonal biomarkers, and the extended longitudinal assessments, which will permit examination of the potential reciprocal effects of sleep disturbance, inflammation, circadian variation in cortisol, and RA symptoms and disease activity. The study team includes a unique collaboration of investigators with expertise in rheumatology, sleep, immunology, psychoneuroimmunology, and statistical methods. Data will yield insights into predictors and mechanistic precursors of sleep disturbance, provide information regarding the impact of sleep disturbance on RA health outcomes, and provide preliminary evidence for potential interventions. Understanding sleep disturbances in RA is important because assessments of RA disease activity, as well as decisions on the use, timing and evaluation of response to RA therapy, may be impacted by concurrent sleep problems. Better understanding of sleep disturbances in RA may lay groundwork for design and conduct of studies to improve therapeutic strategies, which will ultimately improve health and quality of life of persons with RA.